Pim-1 kinase, which is overexpressed in certain kinds of leukemia and prostate cancer, is a serine/threonine kinase that promotes or enhances canceration of cells, exacerbation of cancer cells, resistance to an anticancer agent, and the like by phosphorylating proteins involved in apoptosis or cell cycle control (Cell, 37, pp. 141-150, 1984; EMBO J., 4, pp. 1793-1798, 1985; The International Journal of Biochemistry & Cell Biology, 37, pp. 726-730, 2005; European Journal of Cancer, 44, pp. 2144-2151, 2008). Because of the aforementioned characteristic actions of pim-1 kinase, usefulness of a substance having an inhibitory action against pim-1 kinase as an anticancer agent or the like is expected (refer to Japanese Patent Unexamined Publication (KOKAI) No. 2007-84494, Japanese Patent Unexamined Publication (KOHYO) No. 2009-511499 and the like).
From the aforementioned point of view, several pim-1 kinase inhibitors useful as an anticancer agent have been proposed. Among them, an example of compounds containing a bicyclic nitrogen-containing heteroaryl ring in a fundamental structure includes the 1,2-imidazo[b]pyridazine compounds disclosed in International Patent Publication WO2008/58126. SGI-1776, a typical compound among those disclosed in the aforementioned publication, has been under a clinical trial (phase I) for use as an anticancer agent. Although developments of compounds having the inhibitory activity against pim-1 kinase have been actively conducted as mentioned above, no medicament has yet been launched into the market, and in view of the circumstances, developments of novel compounds having superior activity have still been desired.
As compounds having the indole or 7-azaindole structure, the compounds disclosed in International Patent Publications WO2009/155052 are known. However, as for these compounds, inhibitory action against pim-1 kinase has not been reported. Although this publication discloses compounds having a benzofuran-3-one ring, and also discloses several compounds having hydroxyl group at the 7-position of the benzofuran-3-one ring, it does not disclose any compound having a substituent other than hydroxyl group at the 7-position of the benzofuran-3-one ring. Compounds having the benzofuran-3-one ring with a substituent at the 7-position are disclosed in Journal of Medicinal Chemistry, 45, pp. 1741-1′747, 2002. However, these compounds do not contain a bicyclic nitrogen-containing heteroaryl ring in the fundamental structure.